Transplantation of immortalized CD34+ and CD34-adipose-derived stem cells improve cardiac function and mitigate systemic pro-inflammatory responses

Jong Ho Kim, Seung Cheol Choi, Chi Yeon Park, Jae Hyoung Park, Ji Hyun Choi, Hyung Joon Joo, Soon Jun Hong, Do-Sun Lim

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Adipose-derived stem cells (ADSCs) have the potential to differentiate into various cell lineages and they are easily obtainable from patients, which makes them a promising candidate for cell therapy. However, a drawback is their limited life span during in vitro culture. Therefore, hTERT-immortalized CD34+ and CD34-mouse ADSC lines (mADSCshTERT) tagged with GFP were established. We evaluated the proliferation capacity, multi-differentiation potential, and secretory profiles of CD34+ and CD34-mADSCshTERT in vitro, as well as their effects on cardiac function and systemic inflammation following transplantation into a rat model of acute myocardial infarction (AMI) to assess whether these cells could be used as a novel cell source for regeneration therapy in the cardiovascular field. CD34+ and CD34-mADSCshTERT demonstrated phenotypic characteristics andmulti-differentiation potentials similar to those of primary mADSCs. CD34+ mADSCshTERT exhibited a higher proliferation ability compared to CD34-mADSCshTERT, whereas CD34-mADSCshTERT showed a higher osteogenic differentiation potential compared to CD34+ mADSCshTERT. Primary mADSCs, CD34+, and CD34-mADSCshTERT primarily secreted EGF, TGF-β1, IGF-1, IGF-2, MCP-1, and HGFR. CD34+ mADSCshTERT had higher secretion of VEGF and SDF-1 compared to CD34-mADSCshTERT. IL-6 secretion was severely reduced in both CD34+ and CD34-mADSCshTERT compared to primary mADSCs. Transplantation of CD34+ and CD34-mADSCshTERT significantly improved the left ventricular ejection fraction and reduced infarct size compared to AMI-induced rats after 28 days. At 28 days after transplantation, engraftment of CD34+ and CD34-mADSCshTERT was confirmed by positive Y chromosome staining, and differentiation of CD34+ and CD34-mADSCshTERT into endothelial cells was found in the infarctedmyocardium. Significant decreases were observed in circulating IL-6 levels in CD34+ and CD34-mADSCshTERT groups compared to the AMI-induced control group. Transplantation of CD34-mADSCshTERT significantly reduced circulating MCP-1 levels compared to the AMI control and CD34+ mADSCshTERT groups. GFP-tagged CD34+ and CD34-mADSCshTERT are valuable resources for cell differentiation studies in vitro as well as for regeneration therapy in vivo.

Original languageEnglish
Article numbere0147853
JournalPLoS One
Volume11
Issue number2
DOIs
Publication statusPublished - 2016 Feb 1

Fingerprint

myocardial infarction
cardiac output
Stem cells
stem cells
Rats
Interleukin-6
Stem Cells
Transplantation
inflammation
Myocardial Infarction
Insulin-Like Growth Factor II
Endothelial cells
1-methylcyclopropene
Chromosomes
Insulin-Like Growth Factor I
Epidermal Growth Factor
interleukin-6
therapeutics
Vascular Endothelial Growth Factor A
Regeneration

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Transplantation of immortalized CD34+ and CD34-adipose-derived stem cells improve cardiac function and mitigate systemic pro-inflammatory responses. / Kim, Jong Ho; Choi, Seung Cheol; Park, Chi Yeon; Park, Jae Hyoung; Choi, Ji Hyun; Joo, Hyung Joon; Hong, Soon Jun; Lim, Do-Sun.

In: PLoS One, Vol. 11, No. 2, e0147853, 01.02.2016.

Research output: Contribution to journalArticle

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